High diversity of HHV‐8 molecular subtypes in the Amazon region of Brazil: Evidence of an ancient human infection

Abstract

The present study describes the molecular epidemiology of Human herpesvirus 8 (HHV-8) among four Indian tribes (Kararao, Arara Laranjal, Tiriyo, and Zo'e) of the Amazon region of Brazil and a group of HIV-1-infected subjects from the urban population of Belem, Para. Infection was characterized by the presence of antibodies using ELISA (measuring antibodies to ORF59, ORF65, K8.1A, K8.1B, and ORF73), and molecular assays (gene amplification of the regions ORF26 and the variable region VR1). Antibodies to HHV-8 were detected in 66 samples of the 221 Brazilian Amerindians, namely, 6 (25%) in the Kararao, 18 (19.6%) in the Arara Laranjal, 24 (42.9%) in the Tiriyo, and 18 (36.7%) in the Zo'e. Among the 477 HIV-1-infected subjects, antibodies to HHV-8 were present in 74 (15.5%) persons. The ORF26 region was amplified in seven samples, one of the Arara Laranjal, one of the Tiriyo, two of the Zo'e, and three of the HIV-1-infected group. Subtyping of HHV-8 described a high multiplicity of molecular subtypes, including C (Zo'e), E (Tiriyo), and B (HIV-1 infected). Serological results confirm the high prevalence of HHV-8 among Amerindians and the presence of three subtypes in the Amazon region of Brazil, including a unique subtype, which favors the idea of HHV-8 as an ancient human infection within this particular geographical region.

Genotypic distribution of HHV-8 in AIDS individuals without and with Kaposi sarcoma

“…It is noticeable a predominance of European-American descendants (77.0%), which reflects the predominantly European ancestry of São Paulo patients, with HHV-8 genotypes A, B, C, and F. For the first time we have described the occurrence of genotype F in Brazil, which had been previously described in Bantu tribe of Sub-Saharan Africa. [26] Unlike previous studies demonstrating a high prevalence of HHV-8 genotype A among individuals with AIDS-KS in the United States, Latin America, Northern Europe and Asia, [12,20,21,23,24,48] we have observed a lower prevalence of genotype A in relation to genotypes B and C in both non-KS and KS groups in AIDS individuals, reaching statistical significance particularly in the former group. In fact, our data regarding the predominance of genotypes B and C in Brazilian HHV-8 isolates agree with previous report by Caterino [18] which was based on a small fragment of the ORF-26 gene.…”

“…[9,10,12,14,15] For example, several short targets of HHV-8 from AIDS-KS lesions were selected to identify distinctive molecular pattern, but with restricted coverage of the repertoire of HHV-8 genotypes. [17–19,12,20–23] Nowadays, sequence analysis of highly variable ORF K1 regions (i.e., VR1 and VR2) has allowed the identification of 7 major subtypes or genotypes of HHV-8 (A, B, C, D, E, F, and Z), all exhibiting clear ethnic and geographic clustering. [10,12,15,21,23–27] In addition, the ORF-K1 encodes for a transmembrane signaling molecule that plays an important role in the lifecycle of HHV-8, provoking cellular activation, endothelial cell immortalization and works synergistically with HIV-1 Tat to promote tumors.…”

“…[13,18,21,23,25] Herein, we investigated whether there is an association between HHV-8 variability and development of AIDS-KS by performing a phylogenetic analysis of complete and partial K1 sequences of the HHV-8 genome and profiles of the viral genotype and subgenotype of AIDS individuals without or with KS.…”

Human Herpesvirus 8 Genotype E in Patients with Kaposi Sarcoma, Peru

“…HHV-8 genotype E previously has been found exclusively in Amerindians from Central and South America, including Brazil ( 5 , 9 ), Ecuador ( 7 ), and French Guiana ( 6 ). In each instance, HHV-8 was detected in blood samples, and there was some debate about the presence/development of KS in such highly infected populations ( 15 ).…”

“…A and C subtypes are prevalent in Europe, Mediterranean countries, the United States, northwestern People’s Republic of China, and southern Siberia; subtype B, in sub-Saharan Africa; and subtype D, in Japan and Oceania. Subtype E is found among Native Americans ( 5 – 9 ). To our knowledge, KS has been reported in patients infected by all HHV-8 subtypes, except E.…”